The Efficacy and Safety of Pucotenlimab Combined With TP Chemotherapy as Neoadjuvant Therapy for Locally Advanced HNSCC

Prior treatment

• Concurrent second primary malignancy (e.g., esophageal cancer).
• Participation in another interventional clinical trial or use of investigational drugs within 30 days prior to screening.
• Systemic glucocorticoids (\>10 mg/day prednisone equivalent) or immunosuppressive agents within 14 days prior to randomization.
  • Exceptions: Inhaled/topical steroids or physiologic replacement doses for adrenal insufficiency.
• Active infection requiring treatment or systemic antimicrobial use within 1 week prior to first dose.
• Live vaccines administered within 30 days before first dose or during the study.

Other illness

• Cachexia or multiple organ failure.
• Active autoimmune disease(s) requiring systemic treatment (excluding vitiligo, resolved childhood asthma/atopy, or controlled hypothyroidism on hormone replacement).
• Severe active infection requiring systemic therapy.
• Uncontrolled comorbid medical conditions that may compromise protocol compliance, per investigator judgment, including:
  • Severe cardiovascular/cerebrovascular diseases,
  • Uncontrolled diabetes/hypertension,
  • Active peptic ulcer,
  • Uncontrolled infections.
• Dementia, altered mental status, or cognitive impairment affecting informed consent or questionnaire completion.
• Grade ≥2 hearing impairment (per CTCAE v5.0).
• History of malignancy within the past 5 years (excluding cured non-melanoma skin cancer or carcinoma in situ).
• Known HIV-positive status or AIDS.
• Vulnerable populations (e.g., severe psychiatric disorders, cognitive impairment, critically ill patients, prisoners, pregnant individuals).
• Other conditions deemed by the investigator to preclude safe study participation.

Other

• Grade ≥2 peripheral neuropathy (per CTCAE v5.0).
• Nasopharyngeal carcinoma or squamous cell carcinoma originating outside oral cavity, oropharynx, hypopharynx, or larynx (e.g., sinonasal tract, paranasal sinuses, or unknown primary).
• Pregnancy, breastfeeding, or refusal of contraception by subjects of childbearing potential.

• Age: 18 to 70 years old.
• Diagnosis: Histopathologically confirmed head and neck squamous cell carcinoma (HNSCC) of the oropharynx, oral cavity, hypopharynx, or larynx, classified as Stage III or IV A according to the AJCC Cancer Staging Manual (8th Edition).
• Measurable Disease: At least one measurable primary lesion per RECIST 1.1 criteria.
• Treatment Status: Treatment-naïve patients with no prior therapy for the disease.
• Performance Status: ECOG performance status of 0-1.
• Surgical Eligibility: Deemed eligible for elective standard surgery followed by standard adjuvant chemoradiotherapy/radiotherapy, as assessed by the investigator.
• Autoimmune Disease: No active autoimmune diseases.
• Concurrent Malignancy: No concurrent malignancies.
• Life Expectancy: ≥6 months.
• Biomarker Testing: Available tumor tissue samples for PD-L1 testing via Combined Positive Score (CPS) using 22C3 pharmDx assay (DAKO).
• Hematologic Parameters:
  • ANC ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥100 g/L, WBC ≥3.5×10⁹/L.
  • No transfusion within 7 days or bleeding tendency.
• Liver Function: ALT, AST, ALP, and total bilirubin ≤1.5× upper limit of normal (ULN).
• Renal Function: Serum creatinine ≤1.5× ULN or creatinine clearance \>60 mL/min.
• HPV Status: HPV status confirmed via p16 immunohistochemistry (IHC) and/or in situ hybridization (ISH).
• Informed Consent: Voluntarily participates and signs informed consent. For participants unable to consent due to incapacity, consent must be provided by a legally authorized representative. For illiterate participants, an impartial witness must attest to the informed consent process.